基于网络药理学和分子对接研究三七抗类风湿关节炎的分子机制

doi:10.3976/j.issn.1002-4026.2022.02.005

Abstract

Abstract:

Network pharmacology and molecular docking methods were used to study the molecular mechanism of Notoginseng Radix Et Rhizoma's action against rheumatoid arthritis. The main active ingredients and related targets of Notoginseng Radix Et Rhizoma were obtained through the Traditional Chinese Medicine systems pharmacology database and analysis platform (TCMSP). The GeneCards database was used to predict rheumatoid arthritis-related targets, and the Uniprot database was used to standardize protein names and obtain the intersection target of Notoginseng Radix Et Rhizoma and rheumatoid arthritis. The STRING platform was used to analyze protein-protein interactions, and the Metascape platform was used to perform gene ontology (GO) function analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis. Cytoscape 3.7.2 was used to construct the active ingredient-target-signaling pathway interaction network. In addition, the AutoDock Vina 1.1.2 software was used for molecular docking of key targets and components. On screening, 7 core active ingredients of Notoginseng Radix Et Rhizoma and 100 intersection targets for Notoginseng Radix Et Rhizoma and rheumatoid arthritis, e.g., AKT1, IL6, VEGFA, TNF, TP53, JUN, CASP3, and PTGS2 were obtained. GO and KEGG analyses derived 1064 and 102 signaling pathways, respectively; of which, the signaling pathways related to rheumatoid arthritis included AGE-RAGE, MAPK, TNF, IL-17, and HIF-1 signaling pathways. Furthermore, molecular docking results showed that the key targets and components had a good binding activity. Therefore, our results suggest that Notoginseng Radix Et Rhizoma may play a role in preventing rheumatoid arthritis by the regulation of multiple targets and pathways, such as metabolism, signal transduction, and inflammatory pathways.

Key words: network pharmacology, rheumatoid arthritis, Notoginseng Radix Et Rhizoma, molecular docking

CLC Number:

R285

ZHANG Xiao-wen,YING Tian-hao,LIANG Mei-chen,WANG Yan-fang,WANG Xin-lin,ZHANG Lei-ming. Molecular mechanism of Notoginseng Radix Et Rhizoma's action against rheumatoid arthritis based on network pharmacology and molecular docking[J].Shandong Science, 2022, 35(2): 36-45.

Figures/Tables 11

Table 1

Fig.1

Fig.2

Fig.3

Fig.4

Fig.5

Fig.6

Table 2

Table 3

Table 4

Fig.7

References 31

[1]	MCINNES I B, SCHETT G. Pathogenetic insights from the treatment of rheumatoid arthritis[J]. The Lancet, 2017, 389(10086): 2328-2337. DOI: 10.1016/S0140-6736(17)31472-1. doi: 10.1016/S0140-6736(17)31472-1
[2]	世界中医药学会联合会, 中华中医药学会. 国际中医临床实践指南类风湿关节炎(2019-10-11)[J]. 世界中医药, 2020, 15(20): 3160-3168. DOI: 10.3969/j.issn.1673-7202.2020.20.034. doi: 10.3969/j.issn.1673-7202.2020.20.034
[3]	张靖, 周彬, 王彦丽, 等. 抗类风湿性关节炎中药的研究进展[J]. 中草药, 2013, 44(15): 2189-2194. DOI: 10.7501/j.issn.0253-2670.2013.15.028. doi: 10.7501/j.issn.0253-2670.2013.15.028
[4]	梁荻, 吴金玉, 镇立, 等. 三七治疗类风湿关节炎作用机制的探讨[J]. 风湿病与关节炎, 2018, 7(7): 64-66. DOI: 10.3969/j.issn.2095-4174.2018.07.015. doi: 10.3969/j.issn.2095-4174.2018.07.015
[5]	张洁. 中药三七的药理作用及研究进展[J]. 中国卫生产业, 2017, 14(28): 40-41. DOI: 10.16659/j.cnki.1672-5654.2017.28.040. doi: 10.16659/j.cnki.1672-5654.2017.28.040
[6]	李兰林, 孙晓博, 向大雄. 天然药物中有效成分抗类风湿关节炎研究进展[J]. 中南药学, 2011, 9(2): 130-134. DOI: 10.3969/j.issn.1672-2981.2011.02.016. doi: 10.3969/j.issn.1672-2981.2011.02.016
[7]	陈红艳, 陈安, 卢芳国, 等. 三七总皂苷的药理研究进展[J]. 湖南中医杂志, 2019, 35(1): 154-157. DOI: 10.16808/j.cnki.issn1003-7705.2019.01.066. doi: 10.16808/j.cnki.issn1003-7705.2019.01.066
[8]	汪梦霞, 赵静宇, 孙冬梅, 等. 三七总皂苷对6-羟基多巴胺诱导SH-SY₅Y细胞损伤的保护作用及可能机制[J]. 药学学报, 2016, 51(6): 898-906. DOI: 10.16438/j.0513-4870.2015-1082. doi: 10.16438/j.0513-4870.2015-1082
[9]	张声生, 吴震宇, 陈剑明, 等. 三七总皂苷改善高脂诱导脂肪肝大鼠模型氧化应激及胰岛素抵抗的研究[J]. 中国中西医结合杂志, 2014, 34(1): 56-61. DOI: 10.7661/CJIM.2014.01.0056. doi: 10.7661/CJIM.2014.01.0056
[10]	蔡诗婷, 刘晓颖, 林秋雄, 等. 三七总皂苷抗G/GO诱导的H9c2细胞凋亡与线粒体生物合成的关系研究[C]// 第15届中国南方国际心血管病学术会议论文集.广州:中华医学会, 2013.
[11]	姜辉, 汪永忠, 刘晓闯, 等. 三七总皂苷对肝纤维化大鼠细胞因子的影响[J]. 中药材, 2013, 36(7): 1123-1127. DOI: 10.13863/j.issn1001-4454.2013.07.032. doi: 10.13863/j.issn1001-4454.2013.07.032
[12]	HONG S J, WAN J B, ZHANG Y, et al. Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro and zebrafish in vivo[J]. Phytotherapy Research: PTR, 2009, 23(5): 677-686. DOI: 10.1002/ptr.2705. doi: 10.1002/ptr.2705
[13]	蔡辉, 姚茹冰, 王圆圆. 单味中药及有效成分对类风湿关节炎炎性细胞因子TNF-ɑ的影响[J]. 辽宁中医药大学学报, 2015, 17(12): 5-8. DOI: 10.13194/j.issn.1673-842x.2015.12.001. doi: 10.13194/j.issn.1673-842x.2015.12.001
[14]	张志琴, 朱双雪. 槲皮素的药理活性与临床应用研究进展[J]. 药学研究, 2013, 32(7): 400-403. DOI: 10.13506/j.cnki.jpr.2013.07.011. doi: 10.13506/j.cnki.jpr.2013.07.011
[15]	黄敬群, 孙文娟, 王四旺, 等. 尿酸钠致急性痛风性关节炎模型大鼠与槲皮素的抗炎作用[J]. 中国组织工程研究, 2012, 16(15): 2815-2819. DOI: 10.3969/j.issn.1673-8225.2012.15.034. doi: 10.3969/j.issn.1673-8225.2012.15.034
[16]	刘博, 俞婷, 韩晓蕾, 等. 人参皂苷抗炎作用及其分子机制的研究进展[J]. 中国药学杂志, 2019, 54(4): 253-258.
[17]	HSIEH Y H, DENG J S, CHANG Y S, et al. Ginsenoside Rh2 ameliorates lipopolysaccharide-induced acute lung injury by regulating the TLR4/PI3K/Akt/mTOR, raf-1/MEK/ERK, and Keap1/Nrf2/HO-1 signaling pathways in mice[J]. Nutrients, 2018, 10(9): 1208. DOI: 10.3390/nu10091208. doi: 10.3390/nu10091208
[18]	RAJAVEL T, PACKIYARAJ P, SURYANARAYANAN V, et al. Β-Sitosterol targets Trx/Trx1 reductase to induce apoptosis in A549 cells via ROS mediated mitochondrial dysregulation and p53 activation[J]. Scientific Reports, 2018, 8: 2071. DOI: 10.1038/s41598-018-20311-6. doi: 10.1038/s41598-018-20311-6
[19]	GABAY O, SANCHEZ C, SALVAT C, et al. Stigmasterol: a phytosterol with potential anti-osteoarthritic properties[J]. Osteoarthritis and Cartilage, 2010, 18(1): 106-116. DOI: 10.1016/j.joca.2009.08.019. doi: 10.1016/j.joca.2009.08.019
[20]	刘国栋, 辛兵, 黄栋, 等. 亚油酸乙酯抑制钛颗粒诱导的炎症反应及其作用机制[J]. 中国组织工程研究, 2016, 20(52): 7836-7843. DOI: 10.3969/j.issn.2095-4344.2016.52.012. doi: 10.3969/j.issn.2095-4344.2016.52.012
[21]	PARK S Y, SEETHARAMAN R, KO M J, et al. Ethyl linoleate from garlic attenuates lipopolysaccharide-induced pro-inflammatory cytokine production by inducing heme oxygenase-1 in RAW_264.7 cells[J]. International Immunopharmacology, 2014, 19(2): 253-261. DOI: 10.1016/j.intimp.2014.01.017. doi: 10.1016/j.intimp.2014.01.017
[22]	杜烨湘. 甘草素通过抑制炎症反应对阿尔兹海默病的保护作用及其机制研究[D]. 重庆: 重庆医科大学, 2019.
[23]	孟延丰, 唐敏, 任国卫, 等. 甘草素调控miR-155对骨关节炎软骨细胞增殖和凋亡的影响[J]. 中国临床药理学杂志, 2020, 36(10): 1310-1314. DOI: 10.13699/j.cnki.1001-6821.2020.10.038. doi: 10.13699/j.cnki.1001-6821.2020.10.038
[24]	DUBOIS C, FRADIN C, BOULANGER É. Axe AGE-RAGE: Conséquences physiopathologiques et inflammaging[J]. Médecine Des Maladies Métaboliques, 2019, 13(7): 595-601. DOI: 10.1016/S1957-2557(19)30182-8. doi: 10.1016/S1957-2557(19)30182-8
[25]	韩静, 姚青, 黄黎明, 等. 中药有效部位复方对糖尿病大鼠坐骨神经AGE-RAGE-NFkB-氧化应激的影响[C]// 中华医学会第十一次全国内分泌学学术会议论文汇编. 广州: 中华医学会, 2012.
[26]	石璐, 孙文燕. 基于网络药理学探讨芍药甘草汤治疗类风湿关节炎的作用机制[J]. 中草药, 2020, 51(24): 6246-6257. DOI: 10.7501/j.issn.0253-2670.2020.24.014. doi: 10.7501/j.issn.0253-2670.2020.24.014
[27]	LI N, XU Q, LIU Q P, et al. Leonurine attenuates fibroblast-like synoviocyte-mediated synovial inflammation and joint destruction in rheumatoid arthritis[J]. Rheumatology, 2017, 56(8): 1417-1427. DOI: 10.1093/rheumatology/kex142. doi: 10.1093/rheumatology/kex142
[28]	石慧, 王丹彤, 乌日嘎. TNF-α介导的NF-κB信号通路在类风湿性关节炎血管形成中的作用[J]. 医学综述, 2012, 18(15): 2397-2400. DOI: 10.3969/j.issn.1006-2084.2012.15.019. doi: 10.3969/j.issn.1006-2084.2012.15.019
[29]	曾龙秀, 肖朝文, 孙江阳, 等. 慢性乙型肝炎患者炎症因子表达水平及IL-23/IL-17信号通路的活性变化[J]. 中华医院感染学杂志, 2020, 30(10): 1512-1516. DOI: 10.11816/cn.ni.2020-191552. doi: 10.11816/cn.ni.2020-191552
[30]	SAITO-SASAKI N, SAWADA Y, OMOTO D, et al. A possible pathogenetic role of IL-23/IL-17 axis in rheumatoid nodules in patients with rheumatoid arthritis[J]. Clinical Immunology (Orlando, Fla), 2016, 170: 20-21. DOI: 10.1016/j.clim.2016.07.002. doi: 10.1016/j.clim.2016.07.002
[31]	许炜民, 钱佳佳, 韩龙, 等. 温经通络汤对小鼠膝骨关节炎软骨形态改变和VEGF、MMP-13、HIF-1α表达情况的影响[J]. 中医药信息, 2020, 37(6): 6-12. DOI: 10.19656/j.cnki.1002-2406.200150. doi: 10.19656/j.cnki.1002-2406.200150

编号	代号	中文名称	英文名称	OB/%	DL
MOL001494	SQ1	亚油酸乙酯	mandenol	42.00	0.19
MOL001792	SQ2	甘草素	liquiritigenin	32.76	0.18
MOL002879	SQ3	邻苯二甲酸二异辛酯	diop	43.59	0.39
MOL000358	SQ4	β-谷甾醇	beta-sitosterol	36.91	0.75
MOL000449	SQ5	豆甾醇	stigmasterol	43.83	0.76
MOL005344	SQ6	人参皂苷rh2	ginsenoside rh2	36.32	0.56
MOL000098	SQ7	槲皮素	quercetin	46.43	0.28

标记	编号	名称	连接度	介度	紧密度
SQ7	MOL000098	槲皮素	68	0.341 3	0.744 2
SQ6	MOL005344	人参皂苷rh2	9	0.008 0	0.385 5
SQ4	MOL000358	β-谷甾醇	7	0.000 9	0.373 5
SQ5	MOL000449	豆甾醇	2	0.000 3	0.332 2
SQ1	MOL001494	亚油酸乙酯	1	0.000 0	0.325 4
SQ2	MOL001792	甘草素	1	0.000 0	0.275 1

靶点	连接度	介度	紧密度
AKT1	19	0.018 8	0.533 3
RELA	19	0.018 1	0.533 3
MAPK1	18	0.017 7	0.527 5
IL6	16	0.013 1	0.516 1
CHUK	16	0.011 9	0.510 6
TNF	15	0.013 3	0.510 6
NFKBIA	15	0.012 6	0.510 6
JUN	15	0.013 2	0.510 6
CASP3	15	0.014 7	0.510 6
TP53	14	0.009 4	0.500 0

编号	化合物名称	结合自由能/(kJ·mol^-1)
MOL000098	槲皮素	-6.2
MOL000358	β-谷甾醇	-6.9
MOL000449	豆甾醇	-7.1
MOL001494	亚油酸乙酯	-4.3
MOL001792	甘草素	-6.4
MOL005344	人参皂苷rh2	-7.1

Molecular mechanism of Notoginseng Radix Et Rhizoma's action against rheumatoid arthritis based on network pharmacology and molecular docking

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 11

References 31

Related Articles 15

Metrics

Comments

Recommended 0

[1]	SUN Jingtian, LIU Feng, ZHANG Zhe, ZHANG Yufu, MA Xinhui, LI Qingjun, WANG Xiao, DONG Hongjing. Exploring the medication rule of Chrysanthemum morifolium Ramat. and investigating the synergistic pharmacological activity of core combination herbs [J]. Shandong Science, 2025, 38(1): 1-8.
[2]	HAN Huijie, LIU Hui, ZHAO Yongbo, WANG Songpo. A study based on network pharmacology and experimental verification exploring the mechanism of quercetin against colorectal cancer through the p53 signaling pathway [J]. Shandong Science, 2025, 38(1): 32-43.
[3]	FAN Wei, SHEN Chuanlin, ZHANG Xuanming, DU Xingshuo, ZHAN Wen, SUN Chen, JIN Meng, LI Xiaobin, ZHANG Sichen, SUN Botong, HE Qiuxia. Prediction of anti-aging mechanism of Panax quinquefolius L. by network pharmacology and molecular docking [J]. Shandong Science, 2024, 37(6): 42-50.
[4]	YAN Jin, LI Fei, WU Keming, YANG Haobo. The molecular mechanisms by which Xinjia Cistanche Tusi Decoction promotes follicular development through mitophagy [J]. Shandong Science, 2024, 37(5): 25-34.
[5]	LIN Shenghua, XUE Chang, MA honglin, FAN Wei, SHEN Chuanlin, CHEN Jiayu, SUN Botong, DU Xingshuo, ZHAN Wen, LI Xiaobin, ZHANG Shanshan, JIN Meng, HE Qiuxia. Study of the active components and mechanism of action of antithrombotic Xuefuzhuyu oral liquid based on network pharmacology and molecular docking technology [J]. Shandong Science, 2024, 37(4): 26-33.
[6]	MA Shijing, HE Chunyan, GUAN Tianzhu, YAO Xueshuang, ZHANG Junpeng. Exploration of antihyperlipidemia mechanism of Monopterus albus peptides based on hyperlipidemic zebrafish model and network pharmacology [J]. Shandong Science, 2024, 37(3): 27-38.
[7]	WEI Zekun, YANG Yujie, LIU Shuang, WANG Yan, DONG Hongjing, LIU Chunmei. Reverse mining of Chinese medicine for intervention of liver cancer based on GEO database combined with network pharmacology and molecular docking technology [J]. Shandong Science, 2024, 37(3): 39-47.
[8]	LIU Kechun, WANG Yongcheng, ZANG Xiaohan, XIA Qing, ZHANG Yun, ZHANG Shanshan, SUN Chen. Advancements in network pharmacology and zebrafish modeling for studying traditional Chinese medicine’s effective substances and mechanisms of action [J]. Shandong Science, 2024, 37(2): 29-35.
[9]	FU Zhaoju, CHENG Guo, LIN Dengmei, LI Jun, ZHANG Nannan. Experimental study and network pharmacological analysis of the anti-inflammatory action mechanism of Mahonia bealei (Fort.) Carr. [J]. Shandong Science, 2024, 37(1): 24-31.
[10]	CHEN Chun, QI Daqing, PAN Jingwen. Clinical significance of stromal cell score in gastric cancer and intervention with Weifuchun capsules [J]. Shandong Science, 2023, 36(6): 38-47.
[11]	MU Nana, LIAO Binbin, LI Zhen, LI Jipin, LI Yihua, WANG Ying, CHEN Xubing. Investigating the mechanism of action of Elephantopus scaber L. in the treatment of ulcerative colitis based on network pharmacology and molecular docking [J]. Shandong Science, 2023, 36(6): 48-55.
[12]	WANG Yifan, ZHANG Zhe, TIAN Caijun. Mechanism of Sanhuang Xiexin decoction in treatment of Alzheimer's disease based on network pharmacology and molecular docking method [J]. Shandong Science, 2023, 36(5): 19-26.
[13]	FU Mengya, AO Huihao, BU Chao, PENG Tangyi, WU Deling, HAN Yanquan, HONG Yan. Forecast analysis of the quality markers of Zingiberis Rhizoma based on fingerprints and network pharmacology [J]. Shandong Science, 2023, 36(4): 35-41.
[14]	YIN Zhipeng, GAO Yunyun, LIU Wenwen, GUO Pengbo, ZHAO Yinghui. Exploring the mechanism of Xiangsha Liujunzi Decoction in treating Helicobacter pylori-associated gastritis based on network pharmacology and molecular docking technology [J]. Shandong Science, 2023, 36(4): 52-60.
[15]	SUN Tiefeng, DONG Limin, JIAO Ziqi, WANG Ping. Exploration of the dosing pattern and anti-respiratory syncytial virus mechanism of traditional Chinese medicine based on data mining and network pharmacology [J]. Shandong Science, 2023, 36(3): 1-9.